CuAAC ‘Click Chemistry’ in Synthesis of Peptides and Protein Conjugates

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry has revolutionized the field of peptide and peptidomimetic synthesis by providing a reliable, efficient, and highly selective method for forming 1,2,3-triazole linkages in regioselective manner. This robust reaction enables the conjugation of peptides with various functional groups, enhancing their stability, bioactivity, and therapeutic potential. CuAAC facilitates the creation of cyclic peptides, peptide macrocycles, and peptidomimetics with improved pharmacokinetic properties, which are essential for the drug development. The reaction's compatibility with aqueous environments and tolerance for diverse functional groups make it ideal for bioorthogonal applications, including the modification of peptides in complex biological systems. This chapter highlights the significant applications of CuAAC ‘click chemistry’ in the design and synthesis of innovative peptides and peptidomimetics, emphasizing its impact on advancing peptide therapeutics and biomolecular engineering.